The African trypanosomes produce 5 hydroxytryptophol and tryptophol, suggested sleep mediators, in vitro. Trypanosomes are observed in neural tissue, and animals infected with the African trypanosomes develop severe neurological disturbance denoted by lethargy, increased sleep and coma. These facts suggested that the production of tryptophol by the trypanbsomes in vivo might be responsible for the lethargy and sleep syndrome. The proposed study will investigate (1) the effects of the trypanosome metabolites, tryptophol and 5 hydroxytryptophol on the behavior of Microtus montanus and (2) to determine if sufficient concentrations of these compounds are produced by the trypanosomes, and accumulate in neural tissue to account for the symptoms observed in infected animals. The proposed research will be conducted by determining the minimal dosages of tryptophol and 5 hydroxytryptophol required to induce behavioral changes (i.e., increased sleep) and to correlate these minimal dosages with the rate of synthesis of tryptophol and 5 hydroxytroptophyol by the trypanosomes in vitro. Other metabolites of tryptophan, as well as metabolites of tyrosine and phenylatanine will also be investigated for their pharmacological and behavioral effects. This phase will be followed by in vivo studies using C14 labelled tryptophan and 5 hydroxytryptophan. The metabolism of these two compounds will be compared in normal and infected animals. Of particular interest will be the levels of radioactive tryptophol or 5 hydroxytryptophol in the brains of these animals. The total amounts of tryptophol and 5 hydroxytryptophol in the brains of Microtus will also be determined. Finally, in order to strengthen any possible correlations between the synthesis of tryptophol and 5 hydroxytryptophol by the trypanosomes and the behavioral changes observed in infected animals, various antimetabolites and inhibitors which are known to increase or decrease the tryptophol concentration in vivo will be injected into experimental animals. These compounds should be able to inhibit or exaggerate the behavior changes observed in infected animals.